Treatment for cocaine dependence is a research priority, and innovative treatment approaches are needed. The goal of this application is to investigate the potential of a innovative technology that targets a brain region, rather than a medication, for cocaine abuse. Using a repetitive transcranial magnetic stimulation (rTMS) with a newly developed coil that can reach deeper brain regions (the H1 coil), this proposed application will study the effects of deep rTMS directed at the dorsomedial prefrontal cortex and anterior cingulate. Cocaine abusing subjects will undergo functional imaging studies using Positron Emission Tomography (PET) and Magnetic Resonance Imaging (fMRI). The PET scans will use [18F]FDG to measure regional glucose uptake and the fMRI scans will image the effect of deep rTMS on the blood-oxygen-level dependence response to the color-word stroop task. In addition to imaging, a laboratory model of relapse will be used, in which non-treatment seeking cocaine abusing subjects participate in cocaine self-administration sessions. In this model, cocaine abusing subjects are given the choice to self-administer cocaine in the setting of an alternative reinforcer (money), and the hypothesis is that brain stimulation will reduce cocaine self- administration. While this study is not a clinical trail for rTMS, it uses innovative methods that can provide a rapid assessment of its therapeutic potential. This type of translational work can be performed much more rapidly than a clinical study, in addition to providing information on the mechanism behind the response. PUBLIC HEALTH RELEVANCE: The goal of this study is to evaluate the effect of a new method of transcranial magnetic stimulation on a laboratory relapse. In addition, functional imaging scans will be used to measure the effect of brain stimulation on the prefrontal cortex, and area of the brain that has been implicated in cocaine abuse. The scans will provide a measure of metabolism and blood flow in this brain region, and we will investigate whether these changes play a role in reducing cocaine-seeking behavior.